tbuckley/cabot-search huggingface dataset:
Gut Inflammation in axial Spondyloarthritis patients is characterized by a marked Type 17 skewed mucosal Innate‐like T cell signature
Authors: Céline Mortier, Katrien Quintelier, Ann‐Sophie De Craemer, Thomas Renson, Liselotte Deroo, Emilie Dumas, Eveline Verheugen, Julie Coudenys, Tine Decruy, Zuzanna Lukasik, Sofie Van Gassen, Yvan Saeys, Anne Hoorens, Triana Lobatón, Filip Van den Bosch, Tom Van de Wiele, Koen Venken, Dirk Elewaut
Journal: Arthritis & Rheumatology (2023)

Patients with spondyloarthritis (SpA) often present with microscopic signs of gut inflammation, a risk factor for progressive disease. We investigated whether mucosal innate-like T cells are involved in dysregulated interleukin-23 (IL-23)/IL-17 responses in the gut-joint axis in SpA.Ileal and colonic intraepithelial lymphocytes (IELs), lamina propria lymphocytes (LPLs), and paired peripheral blood mononuclear cells (PBMCs) were isolated from treatment-naive patients with nonradiographic axial SpA with (n = 11) and without (n = 14) microscopic gut inflammation and healthy controls (n = 15) undergoing ileocolonoscopy. The presence of gut inflammation was assessed histopathologically. Immunophenotyping of innate-like T cells and conventional T cells was performed using intracellular flow cytometry. Unsupervised clustering analysis was done by FlowSOM technology. Serum IL-17A levels were measured via Luminex.Microscopic gut inflammation in nonradiographic axial SpA was characterized by increased ileal intraepithelial γδ-hi T cells, a γδ-T cell subset with elevated γδ-T cell receptor expression. γδ-hi T cells were also increased in PBMCs of patients with nonradiographic axial SpA versus healthy controls and were strongly associated with Ankylosing Spondylitis Disease Activity Score. The abundance of mucosal-associated invariant T cells and invariant natural killer T cells was unaltered. Innate-like T cells in the inflamed gut showed increased RORγt, IL-17A, and IL-22 levels with loss of T-bet, a signature that was less pronounced in conventional T cells. Presence of gut inflammation was associated with higher serum IL-17A levels. In patients treated with tumor necrosis factor blockade, the proportion of γδ-hi cells and RORγt expression in blood was completely restored.Intestinal innate-like T cells display marked type 17 skewing in the inflamed gut mucosa of patients with nonradiographic axial SpA. γδ-hi T cells are linked to intestinal inflammation and disease activity in SpA.
Microscopy based methods for characterization, drug delivery, and understanding the dynamics of nanoparticles
Authors: Priyamvada Gupta, Nilesh Rai, Ashish Verma, Vibhav Gautam
Journal: Medicinal Research Reviews (2023)

Nanomedicine is an emerging field that exploits nanotechnology for the development of novel therapeutic and diagnostic modalities. Researches are been focussed in nanoimaging to develop noninvasive, highly sensitive, and reliable tools for diagnosis and visualization in nanomedical field. The application of nanomedicine in healthcare requires in-depth understanding of their structural, physical and morphological properties, internalization inside living system, biodistribution and localization, stability, mode of action and possible toxic health effects. Microscopic techniques including fluorescence-based confocal laser scanning microscopy, super-resolution fluorescence microscopy and multiphoton microscopy; optical-based Raman microscopy, photoacoustic microscopy and optical coherence tomography; photothermal microscopy; electron microscopy (transmission electron microscope and scanning electron microscope); atomic force microscopy; X-ray microscopy and, correlative multimodal imaging are recognized as an indispensable tool in material research and aided in numerous discoveries. Microscopy holds great promise in detecting the fundamental structures of nanoparticles (NPs) that determines their performance and applications. Moreover, the intricate details that allows assessment of chemical composition, surface topology and interfacial properties, molecular, microstructure, and micromechanical properties are also elucidated. With plethora of applications, microscopy-based techniques have been used to characterize novel NPs alongwith their proficient designing and adoption of safe strategies to be exploited in nanomedicine. Consequently, microscopic techniques have been extensively used in the characterization of fabricated NPs, and their biomedical application in diagnostics and therapeutics. The present review provides an overview of the microscopy-based techniques for in vitro and in vivo application in nanomedical investigation alongwith their challenges and advancement to meet the limitations of conventional methods.
Interfacility Transfer of Uninsured vs Insured Patients With ST-Segment Elevation Myocardial Infarction in California
Authors: Michael J. Ward, Sayeh Nikpay, Andrew Shermeyer, Brahmajee K. Nallamothu, Ivan Rokos, Wesley H. Self, Renee Y. Hsia
Journal: JAMA Network Open (2023)

Importance Insurance status has been associated with whether patients with ST-segment elevation myocardial infarction (STEMI) presenting to emergency departments are transferred to other facilities, but whether the facility’s percutaneous coronary intervention capabilities mediate this association is unknown. Objective To examine whether uninsured patients with STEMI were more likely than patients with insurance to experience interfacility transfer. Design, Setting, and Participants This observational cohort study compared patients with STEMI with and without insurance who presented to California emergency departments between January 1, 2010, and December 31, 2019, using the Patient Discharge Database and Emergency Department Discharge Database from the California Department of Health Care Access and Information. Statistical analyses were completed in April 2023. Exposures Primary exposures were lack of insurance and facility percutaneous coronary intervention capabilities. Main Outcomes and Measures The primary outcome was transfer status from the presenting emergency department of a percutaneous coronary intervention–capable hospital, defined as a facility performing 36 percutaneous coronary interventions per year. Multivariable logistic regression models with multiple robustness checks were performed to determine the association of insurance status with the odds of transfer. Results This study included 135 358 patients with STEMI, of whom 32 841 patients (24.2%) were transferred (mean [SD] age, 64 [14] years; 10 100 women [30.8%]; 2542 Asian individuals [7.7%]; 2053 Black individuals [6.3%]; 8285 Hispanic individuals [25.2%]; 18 650 White individuals [56.8%]). After adjusting for time trends, patient factors, and transferring hospital characteristics (including percutaneous coronary intervention capabilities), patients who were uninsured had lower odds of experiencing interfacility transfer than those with insurance (adjusted odds ratio, 0.93; 95% CI, 0.88-0.98; P = .01). Conclusions and Relevance After accounting for a facility’s percutaneous coronary intervention capabilities, lack of insurance was associated with lower odds of emergency department transfer for patients with STEMI. These findings warrant further investigation to understand the characteristics of facilities and outcomes for uninsured patients with STEMI.
Reduced malignant glioblastoma recurrence post-resection through the anti-CD47 antibody and Temozolomide co-embedded in-situ hydrogel system
Authors: Lu Ye, Wei Lv, Weichong He, Shengnan Li, Zhiyi Min, Le Gong, Qi Zhang, Chuanhui Teng, Shanbo Sun, Lingyan Lv, Yi Guo, Hongliang Xin
Journal: Journal of Controlled Release (2023)
Mediation Analysis to Untangle Opposing Associations of High-Dose Docosahexaenoic Acid With IQ and Bronchopulmonary Dysplasia in Children Born Preterm
Authors: Thomas R. Sullivan, Jacqueline F. Gould, Jana M. Bednarz, Andrew J. McPhee, Robert Gibson, Peter J. Anderson, Karen P. Best, Mary Sharp, Jeanie L.Y. Cheong, Gillian F. Opie, Javeed Travadi, Peter G. Davis, Karen Simmer, Carmel T. Collins, Lex W. Doyle, Maria Makrides
Journal: JAMA Network Open (2023)

Importance High-dose omega-3 docosahexaenoic acid (DHA) supplementation of children born at less than 29 weeks’ gestation has been shown to improve IQ despite increasing the risk of bronchopulmonary dysplasia (BPD). Given that BPD is associated with poorer cognitive outcomes, it is unclear whether the increased risk of BPD with DHA supplementation is associated with decreased benefit to IQ. Objective To investigate whether the increased risk of BPD with DHA supplementation was associated with diminished IQ benefit. Design, Setting, and Participants This cohort study used data collected from a multicenter, blinded, randomized controlled trial of DHA supplementation in children born at less than 29 weeks’ gestation. Participants were recruited from 2012 to 2015 and followed up until 5 years’ corrected age. Data were analyzed from November 2022 to February 2023. Interventions Enteral DHA emulsion (60 mg/kg/d, to match the estimated in-utero requirement) or a control emulsion from the first 3 days of enteral feeds until 36 weeks’ postmenstrual age or discharge home. Main Outcomes and Measures Physiological BPD was assessed at 36 weeks’ postmenstrual age. IQ was assessed at 5 years’ corrected age using the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition ; children from the 5 highest-recruiting Australian hospitals were assessed. The total effect of DHA supplementation on IQ was divided into direct and indirect effects using mediation analysis, with BPD as the presumed mediating variable. Results Among 656 surviving children from hospitals involved in IQ follow-up (mean [SD] gestational age at birth, 26.8 [1.4] weeks; 346 males [52.7%]), there were 323 children with DHA supplementation and 333 children in the control group. Mean IQ was 3.45 points (95% CI, 0.38 to 6.53 points) higher in the DHA group than the control group, despite an increase in the risk of BPD (160 children [49.7%] vs 143 children [42.8%] with BPD). The indirect effect of DHA on IQ via BPD was not statistically significant (−0.17 points; 95% CI, −0.62 to 0.13 points), with most of the effect of DHA on IQ occurring independently of BPD (direct effect = 3.62 points; 95% CI, 0.55 to 6.81 points). Conclusions and Relevance This study found that associations of DHA with BPD and IQ were largely independent. This finding suggests that if clinicians supplement children born preterm with high-dose DHA, any resulting increase in BPD risk would not be associated with meaningful reductions in the IQ benefit.
Zeolitic imidazolate frameworks: From bactericidal properties to tissue regeneration
Authors: Mehraneh Kermanian, Samad Nadri, Parvin Mohammadi, Siavash Iravani, Nahid Ahmadi, Vajihe Alinezhad, Mohammad-Ali Shokrgozar, Mahdi Haddad, Ebrahim Mostafavi, Aziz Maleki
Journal: Journal of Controlled Release (2023)
Risk of Rabies and Implications for Postexposure Prophylaxis Administration in the US
Authors: Kelly Charniga, Yoshinori Nakazawa, Jen Brown, Seonghye Jeon, Ryan M. Wallace
Journal: JAMA Network Open (2023)

Importance In the US, rabies postexposure prophylaxis (PEP) is often administered without a comprehensive and regionally appropriate rabies risk assessment. For low-risk exposures, this can result in patients incurring out-of-pocket expenses or experiencing adverse effects of PEP unnecessarily. Objective To use a model to estimate (1) the probability that an animal would test positive for rabies virus (RABV) given that a person was exposed, and (2) the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP, and to propose a risk threshold for recommending PEP according to model estimates and a survey. Design, Setting, and Participants In this decision analytical modeling study, positivity rates were calculated using more than 900 000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from a subset of the surveillance data and the literature. Probabilities were estimated using Bayes’ rule. A survey was administered among a convenience sample of state public health officials in all US states (excluding Hawaii) plus Washington, DC and Puerto Rico to determine a risk threshold for PEP recommendation. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology. Main Outcomes and Measures A quantitative and regionally appropriate approach for helping health care practitioners and public health professionals determine whether to recommend and/or administer rabies PEP. Results A total of 1728 unique observations were obtained from the model for the probability that an animal would test positive for RABV given that a person was exposed, and 41 472 for ) the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP. The median probability that an animal would test positive for RABV given that a person was exposed ranged from 3 × 10 −7 to 0.97, while the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP ranged from 1 × 10 −10 to 0.55. Fifty public health officials out of a target sample size of 102 responded to the survey. Using logistic regression, a risk threshold was estimated for PEP recommendation of 0.0004; PEP may not be recommended for exposures with probabilities below this threshold. Conclusions and Relevance In this modeling study of rabies in the US, the risk of death|exposure was quantified and a risk threshold was estimated. These results could be used to inform the decision-making process as to the appropriateness of recommending rabies PEP.
Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study
Authors: Jeffrey L. Neul, Alan K. Percy, Timothy A. Benke, Elizabeth M. Berry-Kravis, Daniel G. Glaze, Eric D. Marsh, Tim Lin, Serge Stankovic, Kathie M. Bishop, James M. Youakim
Journal: Nature Medicine (2023)

Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome. In this phase 3 study ( https://clinicaltrials.gov identifier NCT04181723 ), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks. For the coprimary efficacy endpoints, least squares mean (LSM) change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire for trofinetide versus placebo was -4.9 versus -1.7 (P = 0.0175; Cohen's d effect size, 0.37), and LSM Clinical Global Impression-Improvement at week 12 was 3.5 versus 3.8 (P = 0.0030; effect size, 0.47). For the key secondary efficacy endpoint, LSM change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist Social Composite score was -0.1 versus -1.1 (P = 0.0064; effect size, 0.43). Common treatment-emergent adverse events included diarrhea (80.6% for trofinetide versus 19.1% for placebo), which was mostly mild to moderate in severity. Significant improvement for trofinetide compared with placebo was observed for the coprimary efficacy endpoints, suggesting that trofinetide provides benefit in treating the core symptoms of Rett syndrome.
Rare Lymphomas: Getting “a Bit Ahead”
Journal: Cancer Discovery (2023)

Abstract According to data from the phase III IELSG37 trial, consolidation radiotherapy is unnecessary for patients with primary mediastinal B-cell lymphoma who respond completely to standard immunochemotherapy. Two other studies of peripheral T-cell lymphomas and adult T-cell leukemia/lymphoma, respectively, point to golidocitinib, an investigational JAK1 inhibitor, and mogamulizumab, which targets CCR4, as potential new treatment options.
Intranasal administration of edaravone nanoparticles improves its stability and brain bioavailability
Authors: Yuan Lu, Julie Tzu-Wen Wang, Na Li, Xiaoqin Zhu, Yongjun Li, Sukhi Bansal, Yonglin Wang, Khuloud T. Al-Jamal
Journal: Journal of Controlled Release (2023)

The clinical application of EDV, a potent antioxidant drug approved for amyotrophic lateral sclerosis (ALS), is limited by its short biological half-life and poor water solubility necessitating hospitalization during intravenous infusion. Nanotechnology-based drug delivery constitutes a powerful tool through inferring drug stability and targeted drug delivery improving drug bioavailability at the diseased site. Nose-to-brain drug delivery offers direct access to the brain bypassing the blood brain barrier and reducing systemic biodistribution. In this study, we designed EDV-loaded poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles (NP-EDV) for intranasal administration. NPs were formulated by the nanoprecipitation method. Morphology, EDV loading, physicochemical properties, shelf-life stability, in vitro release and pharmacokinetic assessment in mice were conducted. EDV was efficiently loaded into ∼90 nm NPs, stable up to 30 days of storage, at ∼3% drug loading. NP-EDV reduced H
<i>Erratum:</i> Vol. 72, No. 15
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

on page 414, in the graph, the error bars for the Black or African American, NH category should have denoted a 95% CI of 1.1-1.3 and for the White, NH category should have denoted a 95% CI of 0.4-0.5.
Pediatric Drug and Other Shortages in the Age of Supply Chain Disruption
Authors: Carmel Shachar, Philip A. Gruppuso, Eli Y. Adashi
Journal: JAMA (2023)

This Viewpoint lists the top 3 pediatric drugs and product shortages, considers the federal government’s and manufacturers’ ethical duty to protect children, reviews the causes for the shortages, and suggests policy changes that could help fill in the gap.
Increasing the Reporting Quality of Clinical Trials—No Easy Solutions?
Authors: Nicholas J. DeVito
Journal: JAMA Network Open (2023)

Benjamin Speich, PhD; Erika Mann, BA; Christof M. Schönenberger, MD; Katie Mellor, PhD; Alexandra N. Griessbach, MSc; Paula Dhiman, PhD; Pooja Gandhi, PhD; Szimonetta Lohner, PhD; Arnav Agarwal, MD; Ayodele Odutayo, MD, PhD; Iratxe Puebla, PhD; Alejandra Clark, PhD; An-Wen Chan, MD, DPhil; Michael M. Schlussel, PhD; Philippe Ravaud, MD, PhD; David Moher, MSc, PhD; Matthias Briel, MD, MSc; Isabelle Boutron, MD, PhD; Sara Schroter, PhD; Sally Hopewell, MSc, DPhil
B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation
Authors: Kongyang Ma, Wenhan Du, Shiyun Wang, Fan Xiao, Jingyi Li, Jie Tian, Yida Xing, Xiaodan Kong, Ke Rui, Rencai Qin, Xiaoxia Zhu, Jing Wang, Cainan Luo, Haijing Wu, Yun Zhang, Chengping Wen, Lan He, Dongzhou Liu, Hejian Zou, Qianjin Lu, Lijun Wu, Liwei Lu
Journal: Cellular and Molecular Immunology (2023)
Use of Quantile Treatment Effects Analysis to Describe Antidepressant Response in Randomized Clinical Trials Submitted to the US Food and Drug Administration
Authors: William U. Meyerson, Carl F. Pieper, Rick H. Hoyle
Journal: JAMA Network Open (2023)

Importance Major depressive disorder (MDD) is a leading cause of global distress and disability. Earlier studies have indicated that antidepressant therapy confers a modest reduction in depressive symptoms on average, but the distribution of this reduction requires more research. Objective To estimate the distribution of antidepressant response by depression severity. Design, Setting, and Participants In this secondary analysis of pooled trial data, quantile treatment effect (QTE) analysis was conducted from the US Food and Drug Administration (FDA) database of antidepressant monotherapy for patients with MDD, encompassing 232 positive and negative trials submitted to the FDA between 1979 and 2016. Analysis was restricted to participants with severe MDD (17-item Hamilton Rating Scale for Depression [HAMD-17] score ≥20). Data analysis was conducted from August 16, 2022, to April 16, 2023. Intervention Antidepressant monotherapy compared with placebo. Main Outcomes and Measures The distribution of percentage depression response was compared between the pooled treatment arm and pooled placebo arm. Percentage depression response was defined as 1 minus the ratio of final depression severity to baseline depression severity, expressed as a percentage. Depression severity was reported in HAMD-17-equivalent units. Results A total of 57 313 participants with severe depression were included in the analysis. There was no significant imbalance in baseline depression severity between the pooled treatment arm and pooled placebo arm, with a mean HAMD-17 difference of 0.037 points ( P = .11 by Wilcoxon rank sum test). An interaction term test for rank similarity did not reject the rank similarity governing percentage depression response ( P &amp;amp;gt; .99). The entire distribution of depression response was more favorable in the pooled treatment arm than in the pooled placebo arm. The maximum separation between treatment and placebo occurred at the 55th quantile and corresponded to an absolute improvement in depression due to active drug of 13.5% (95% CI, 12.4%-14.4%). The separation between treatment and placebo diminished near the tails of the distribution. Conclusions and Relevance In this QTE analysis of pooled clinical trial data from the FDA, antidepressants were found to confer a small reduction in depression severity that was broadly distributed across participants with severe depression. Alternatively, if the assumptions behind the QTE analysis are not met, then the data are also compatible with antidepressants eliciting more complete response in a smaller subset of participants than is suggested by this QTE analysis.
When I use a word . . . Medical slang
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

The word “slang,” defined in the <i>Oxford English Dictionary</i> as “The special vocabulary used by any set of persons of a low or disreputable character; language of a low and vulgar type,” and first recorded in 1756, has been thought to be derived from “sling,” which itself comes from an IndoEuropean root SLENG, meaning to slide or sling, to hurl or throw, as it were language that is hurled. However, the evidence that supports this contention is tenuous and the true origin of the word is not known.